Protection by benzamil against dysfunction and damage in rat myocardium after calcium depletion and repletion.
Perfusion of the rat right ventricular wall muscle for 4 min with a Ca2(+)-free medium followed by perfusion with a Ca2(+)-containing solution resulted in a 42% recovery of developed tension, contracture, and a massive release of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) from the muscle. High concentrations (1-5 mM) of amiloride partially protected the ventricular wall from Ca2+ paradox-induced dysfunction. The inclusion of benzamil, an amiloride analogue, 2 min before and during the Ca2(+)-free perfusion period prevented contracture development, restored force development, and almost totally eliminated the release of CPK and LDH from the muscle. Contractile function was best protected by 10-50 microM benzamil. The results demonstrate the efficacy of benzamil as a protective agent against Ca2+ paradox-induced myocardial dysfunction and damage. In view of the known capacity of benzamil to block transsarcolemmal Na(+)-Ca2+ exchange, this study supports the involvement of elevated intracellular Na+ and a stimulation of Na(+)-Ca2+ exchange in this model of cardiac pathology.
Pierce
G N
GN
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Maddaford
T G
TG
Kroeger
E A
EA
Cragoe
E J
EJ
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
C013407:benzamil; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D002118:Calcium